The combination of pyrotinib and capecitabine is a promising strategy in HER2+ breast cancer with brain metastases, as shown by the prospective phase 2 trial PERMEATE recently published on The Lancet Oncology.
After treatment with trastuzumab, approximately 30–50% of patients with HER2+ metastatic breast cancer develop brain metastases usually treated with local therapy, but recurrences are common: a systemic therapy could control both intracranial and extracranial metastases, thus it could be preferable. In this multicenter, single-arm phase 2 trial, authors tested pyrotinib, an oral irreversible tyrosine kinase inhibitor, and capecitabine in 78 patients with HER2+ breast cancer and brain metastases: 59 were radiotherapy-naïve (cohort A), 19 had progressive disease after radiotherapy (cohort B). In both cohorts, patients received pyrotinib and capecitabine as 21-day cycle. The median follow-up was 15.7 months, and the intracranial objective response rate was 74.6% for cohort A and 42.1% for cohort B; there was also a central nervous system objective response in 13 patients of cohort A and 6 patients of cohort B; the median progression-free survival was 11.3 months vs 5.6 months in each cohort, respectively. Data showed that pyrotinib plus capecitabine is well tolerated and active for both intracranial and extracranial lesions, especially for patients with radiotherapy-naive brain metastases, with adverse events consistent with the known toxicity profile of pyrotinib plus capecitabine. Results of this phase 2 study provide evidence of promising antitumor activity for this combination in patients with HER2+ metastatic breast cancer and brain metastases, especially in those with radiotherapy-naive brain metastases, thus warranting further validation through randomized and controlled clinical research.
